The Molecular Genetics of High Myopia

描述（由申请人提供）：拟议的应用程序是一个全面的研究工作的一部分，以分子定义与严重近视或近视有关的人类基因。当聚焦的图像福尔斯在眼睛的视网膜感光层之前时发生近视。近视是人类最常见的眼部疾病，严重的情况下可能导致致盲性疾病，如过早白内障、青光眼、视网膜脱离和黄斑变性。近视是一个巨大的公共卫生问题，并已被列为美国第四大致盲原因。虽然存在以近视为临床特征的遗传综合征，但近视确实以遗传方式作为一种孤立的状况发生。有大量证据表明，遗传因素在非综合征型高度近视的发展中起着重要作用。本实验室定位了3个常染色体显性遗传高度近视位点（MYP 2-染色体18p11.31、MYP 3-染色体12q23.1-q24和染色体17 q21-q22），并进一步完善了X连锁高度近视位点（MYP 1-染色体Xq 28）。该提案的具体目的是：1）识别和招募高度近视家庭，以绘制和完善现有的近视位点; 2）使用位置候选基因筛选方法识别MYP 2基因。MYP 2基因的鉴定将有助于确定经典高度近视的遗传基础，并可能为近视的分子基础提供见解。近视基因突变的确定将有助于我们对眼睛生长发育的理解，并为检查其他屈光疾病的遗传病因提供框架。识别近视易感性的相关基因将提供近视如何发生的基本分子理解，并可能导致定向生理（即药理学，基因治疗）干预。这一努力将有助于我们的长期目标，即为这种潜在致盲性眼病的严重形式制定诊断和治疗策略，目前还没有有效的治疗方法。

DESCRIPTION (provided by applicant): The proposed application is part of a comprehensive research effort to molecularly define human genes that are implicated in severe nearsightedness, or myopia. Myopia occurs when the focused image falls anterior to the retinal photoreceptor layer of the eye. Myopia is the most common human eye disease, and severe cases may lead to blinding disorders such as premature cataracts, glaucoma, retinal detachment, and macular degeneration. Myopia is an enormous public health problem, and has been cited as the 4th leading cause of blindness in the United States. While there are genetic syndromes with myopia as a clinical feature, myopia does occur in an inherited fashion as an isolated condition. There is substantial evidence that genetic factors play a significant role in the development of non-syndromic high myopia. Our laboratory has mapped three autosomal dominant high myopia loci (MYP2- chromosome 18p11.31, MYP3 - chromosome 12q23.1-q24, and a locus at chromosome 17q21-q22), and refined the X-linked high myopia locus (MYP1 at chromosome Xq28). The Specific Aims of this proposal are to: 1) identify and recruit families with high myopia to map and refine existing myopia loci; and 2) identify the MYP2 gene using a positional candidate gene screening approach. Identification of the MYP2 gene will help define the genetic basis of classic high myopia, and may provide insight into the molecular basis of myopia. The determination of myopia gene mutations will contribute to our understanding of eye growth and development, as well as provide a framework for examining the genetic etiology of other refractive disorders. Identifying the implicated genes for myopia susceptibility will provide a fundamental molecular understanding of how myopia occurs, and may lead to directed physiologic (i.e. pharmacologic, gene therapy) interventions. This effort will contribute to our long-term goal to devise diagnostic and therapeutic strategies for the severe forms of this potentially blinding eye disease, which presently has no effective treatment.